Differentiated and exponentially growing HL60 cells exhibit different sensitivity to some genotoxic agents in the comet assay

Montag, Gracia; Bankoglu, Ezgi Eyluel; Bolte, Annika; Hintzsche, Henning; Djelić, Ninoslav; Stopper, Helga

doi:10.1016/j.mrgentox.2018.10.004

Cited by 2 publications

(2 citation statements)

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“…The increase in the DNA-damaging sensor GADD45A is not unexpected in U-2OS/DX30 and U-2OS/DX100 variants, which are continuously exposed to Dox, an inhibitor of topoisomerase 2 and an inducer of DNA strand breaks [ 46 ]. The acute increase of GADD45A is usually associated to apoptosis in osteosarcoma [ 47 , 48 ], but its prolonged increase is a compensatory response to chemotherapeutic drugs and is related to the acquisition of resistance to methotrexate [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Small Nucleolar RNAs Determine Resistance to Doxorubicin in Human Osteosarcoma

Godel

Morena

Ananthanarayanan

et al. 2020

IJMS

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Doxorubicin (Dox) is one of the most important first-line drugs used in osteosarcoma therapy. Multiple and not fully clarified mechanisms, however, determine resistance to Dox. With the aim of identifying new markers associated with Dox-resistance, we found a global up-regulation of small nucleolar RNAs (snoRNAs) in human Dox-resistant osteosarcoma cells. We investigated if and how snoRNAs are linked to resistance. After RT-PCR validation of snoRNAs up-regulated in osteosarcoma cells with different degrees of resistance to Dox, we overexpressed them in Dox-sensitive cells. We then evaluated Dox cytotoxicity and changes in genes relevant for osteosarcoma pathogenesis by PCR arrays. SNORD3A, SNORA13 and SNORA28 reduced Dox-cytotoxicity when over-expressed in Dox-sensitive cells. In these cells, GADD45A and MYC were up-regulated, TOP2A was down-regulated. The same profile was detected in cells with acquired resistance to Dox. GADD45A/MYC-silencing and TOP2A-over-expression counteracted the resistance to Dox induced by snoRNAs. We reported for the first time that snoRNAs induce resistance to Dox in human osteosarcoma, by modulating the expression of genes involved in DNA damaging sensing, DNA repair, ribosome biogenesis, and proliferation. Targeting snoRNAs or down-stream genes may open new treatment perspectives in chemoresistant osteosarcomas.

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Section: Discussionmentioning

confidence: 99%

Small Nucleolar RNAs Determine Resistance to Doxorubicin in Human Osteosarcoma

Godel

Morena

Ananthanarayanan

et al. 2020

IJMS

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“…Montag et al [11] were concerned not with cell/tissue type, but with the state of differentiation of cells -specifically, human promyelocytic HL60 cells which can be induced to differentiate to granulocytelike cells on treatment with DMSO. Tested with H 2 O 2 or KBrO 3 , differentiated and undifferentiated cells showed similar levels of DNA damage.…”

Section: Model Cell Systemsmentioning

confidence: 99%